title: Specific receptor usage in Plasmodium falciparum cytoadherence is associated with disease outcome.
abstract: Our understanding of the basis of severe disease in malaria is incomplete. It is clear that pathology is in part related to the pro-inflammatory nature of the host response but a number of other factors are also thought to be involved, including the interaction between infected erythrocytes and endothelium. This is a complex system involving several host receptors and a major parasite-derived variant antigen (PfEMP1) expressed on the surface of the infected erythrocyte membrane. Previous studies have suggested a role for ICAM-1 in the pathology of cerebral malaria, although these have been inconclusive. In this study we have examined the cytoadherence patterns of 101 patient isolates from varying clinical syndromes to CD36 and ICAM-1, and have used variant ICAM-1 proteins to further characterise this adhesive phenotype. Our results show that increased binding to CD36 is associated with uncomplicated malaria while ICAM-1 adhesion is raised in parasites from cerebral malaria cases.
authors.affiliation: KEMRI/Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Kilifi, Kenya. laochola@gmail.com
authors.forename: Lucy B
authors.initials: LB
authors.lastname: Ochola
authors.forename: Bethsheba R
authors.initials: BR
authors.lastname: Siddondo
authors.forename: Harold
authors.initials: H
authors.lastname: Ocholla
authors.forename: Siana
authors.initials: S
authors.lastname: Nkya
authors.forename: Eva N
authors.initials: EN
authors.lastname: Kimani
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.forename: Johnstone O
authors.initials: JO
authors.lastname: Makale
authors.forename: Anne
authors.initials: A
authors.lastname: Liljander
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
authors.forename: Pete C
authors.initials: PC
authors.lastname: Bull
authors.forename: Tadge
authors.initials: T
authors.lastname: Szestak
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Alister G
authors.initials: AG
authors.lastname: Craig
mesh_terms: D018955:CD36 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006790:Host-Parasite Interactions; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000473:pathology; D010963:Plasmodium falciparum / Q000166:cytology* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D018955:CD36 Antigens; D018799:Intercellular Adhesion Molecule-1